Chandra Sekhar Vasam

Regioselective synthesis of isoxazole-mercaptobenzimidazole hybrids and their in vivo analgesic and anti-inflammatory activity studies.

Regioselective synthesis of isoxazole-mercaptobenzimidazole hybrids and their efficiency in in vivo analgesic and anti-inflammatory activity was described. A comparison of structure-activity relationship for there compounds was also emphasized.

Synthesis of Markovnikov vinyl sulfides via dinuclear Rh(I)-phosphine catalyzed hydrothiolation of alkynes in aqueous media

An efficient and green procedure for the synthesis of Markovnikov i.e. branched vinyl sulfides in aqueous media was developed by employing the dinuclear Rh(I) complexes of hydrophilic phosphines as catalysts in the alkyne hydrothiolation with aliphatic thiols. Deuterium-labeling studies provide evidence for the aptness of these dinuclear catalysts to form selectively the Markovnikov syn-addition products. Catalyst order experiments disclose that the order with respect to the concentration of the catalyst is one, i.e. in solution the active catalyst is dinuclear with one active metal center and the second metal center contribute the cooperative effects to influence the Markovnikov selectivity in hydrothiolation. Further, the possibility of catalyst recovery and recycling experiments were also demonstrated.

Pd-N-heterocyclic carbene catalyzed synthesis of piperidine alkene–alkaloids and their anti-cancer evaluation

A facile synthesis of piperidine alkene-alkaloids including natural (+)-Caulophyllumine B in high yields has been developed by Heck cross-coupling reaction catalyzed by simple in situ formed palladium-N-heterocyclic carbenes (Pd-NHCs). Formation of Pd(0) nanoparticles has been noticed during the reaction course. The synthesized piperidine alkene-alkaloids were evaluated for in vitro anti-cancer activity against a panel of human tumor cell lines of lung, breast and ovarian. Several of these piperidine alkene-alkaloids were found to possess highest growth inhibition activity than the standard drug cisplatin and support the concept to modulate drug receptor interaction.

Silver(I)–N-heterocyclic carbene catalyzed multicomponent reactions: a facile synthesis of multisubstituted pyridines

A four component one-pot reaction between aromatic aldehyde, malononitrile, ammonium acetate and ketone mediated by Ag(I) N-heterocyclic carbene to produce multisubstituted and fused pyridines in a short reaction time (∼10 min) in ethanol at room temperature is described.

Synthesis and anti-cancer evaluation of steroidal diglycoside–pyrazoline hybrids

A new series of steroidal glycoside pyrazoline functional hybrid constructs (SG–pyrazolines 3a–k) synthesized were evaluated for in vitro anti-cancer cytotoxic activity against a panel of human tumor cell lines of lung, breast, CNS, colon and ovarian cancer. These hybrid constructs were also measured at their respective IC50 values on normal cell lines of HMEC and CHO for evaluating the biocompatibility. Several of these new hybrid constructs were found to possess higher growth inhibition activity than the standard cisplatin and support the concept to modulate drug receptor interaction. Regarding the synthesis, firstly a new SG molecule, an extract of Caralluma gracillis, was converted to the chalcones (2a–k) via the condensation of sp3 C–H bonds on methyl keto of the D-ring of SG with appropriate substituted benzaldehydes. The cyclocondensation of SG–chalcones (2a–k) with hydrazine specifically catalyzed by Ag(I) N-heterocyclic carbene (Ag(I)–NHC) in ethanol has produced selectively the SG–pyrazoline hybrids (3a–k).

Synthesis characterization and hydroformylation activity of new mononuclear rhodium(I) compounds incorporated with polar-group functionalized phosphines

A first effort employing a range of polar-group functionalized phosphines (L1–L7) to design mononuclear Rh(I) compounds of [Rh(quin-8-O)(CO)(L)] (quin-8-O = 8-hydroxy quinolate) is described. The reaction of a Rh(I) precursor [Rh(μ-Cl)(CO)2]2 with 8-hydroxyquinoline in the presence of a base followed by phosphines (L1–L7) produced only a single isomer of [Rh(quin-8-O)(CO)(L)] compounds (1–7) with pendant, i.e. non-bonded, polar-groups (includes carboxyl, hydroxyl and formyl). A relationship between Δgd31P chemical shifts and the ν(C≡O) was derived to evaluate and explain the σ-donor properties of these phosphines with respect to the electronic properties of the polar groups and the extent of π-back-bonding to the CO group. These mononuclear Rh(I)-Phosphines were investigated as catalysts in the hydroformylation of 1-hexene and cyclohexene in aqueous two-phase and single-phase solvent systems. The Rh(I) catalysts with strong σ-donor and hydrophilic phosphines provided better yields and selectivities for the hydroformylation products, which is a reverse trend compared to literature reports. When the Rh(I) compounds contained strong σ-donor phosphines, the π-acceptor properties of the pyridine ring of 8-hydroxyquinolate were found to be beneficial for the facile cleavage of the CO group during hydroformylation, and additionally, to improve the kinetic stability of catalysts.

Regioselective synthesis of some new 1,4-disubstituted sulfonyl-1,2,3-triazoles and their antibacterial activity studies

Some new 1,4-disubstituted-sulfonyl-1,2,3-triazoles (3a–f, 5a–h, 7a–d, and 9a–e) were regioselectively synthesized in high yields by Cu(I) catalyzed 1,3-dipolar cycloaddition (DC) reaction of p-acetamidobenzenesulfonyl azide (p-ABSA) with terminal alkynes. These new triazole compounds were evaluated for in vitro antibacterial activity against a panel of Gram-positive Bacillus sphericus, Staphylococcus epidermidis, and Gram-negative Klebsiella pneumonia, Escherichia coli species. Several of these compounds were found to possess comparable growth inhibition activity with the commercial standards Penicillin-G and Streptomycin.

Synthesis and biological evaluation of 4β-benzoxazolepodophyllotoxin hybrids as DNA topoisomerase-II targeting anticancer agents

A series of new 4β-benzoxazolepodophyllotoxin compounds (9a–j) were prepared and screened for cytotoxicity against four human tumour cell lines (HeLa, DU-145, A-159 and MCF-7). Among these compounds, 9a, 9c, 9f and 9i have shown more potent anticancer activity than etoposide with considerable IC50 values. Apoptosis evaluation studies were performed using the Hoechst-33258 staining method and it was found specially that the best active compound 9i shows clear nuclear damage compared to etoposide. Molecular docking studies were also carried out to recognize the interactions against DNA topoisomerase-II and it was found that the energy calculations were in good agreement with the observed IC50 value.

An organo-NHC catalyzed domino addition approach for the selective synthesis of 5-butynylisoxazoles and subsequent Sonogashira coupling

A nucleophilic organo N-heterocyclic carbene (NHC) catalysed click-type fast domino addition of allenyl-MgBr to aryl nitrile oxides to produce 5-butynylisoxazoles with excellent selectivity and good yields is reported. The unwanted protonation and subsequent formation of 5-methylisoxazole byproducts is successfully suppressed. Furthermore, a Pd/Ag catalysed protocol for Sonogashira cross-coupling of 5-butynylisoxazoles to obtain the corresponding internal alkynes with high selectivity and yields is developed by minimising the alkyne homo-coupling.